Topic
Total synthesis
About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.
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TL;DR: In this paper, the Wieland−Miescher ketone was used as a matrix to provide the C and D rings of the targets and to provide functionality implements for joining this sector to an A ring precursor.
Abstract: An intramolecular Heck reaction (90 → 91) serves as the key step in the total synthesis of the titled compounds. The synthetic route is based on utilizing the Wieland−Miescher ketone (5) as a matrix to provide the C and D rings of the targets and to provide functionality implements for joining this sector to an A ring precursor (6). Catalytically induced enantiotopic control and early emplacement of the oxetane are other features of the route.
353 citations
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TL;DR: An extension of the native chemical ligation method to the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin, by using an alkanesulfonamide “safety-catch” linker to circumvent the incompatibility of glycosidic linkages with Boc chemistry.
Abstract: The technique of native chemical ligation has enabled the total chemical synthesis of proteins with molecular weights far in excess of those achievable by conventional stepwise solid-phase peptide synthesis. The method involves the condensation of two unprotected peptide segments, one bearing a C-terminal αthioester and the other an N-terminal cysteine residue, to afford a protein with a native amide linkage at the site of ligation. Here we report an extension of the native chemical ligation method to the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin. The major challenge in our synthesis was preparation of a 24-residue glycopeptide-αthioester segment, which was complicated by the incompatibility of glycosidic linkages with Boc chemistry and by the incompatibility of thioesters with Fmoc chemistry. The use of an alkanesulfonamide “safety-catch” linker circumvented this problem and permitted the solid-phase synthesis of the glycopeptide-αthioester using standa...
351 citations
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TL;DR: The first enantioselective organocatalytic Mukaiyama-Michael reaction using alpha,beta-unsaturated aldehydes has been accomplished and the use of iminium catalysis has provided a new strategy for the enantiOSElective addition of 2-silyloxy furans to unsaturated aaldehydes to generate a variety of butenolide systems.
Abstract: The first enantioselective organocatalytic Mukaiyama−Michael reaction using α,β-unsaturated aldehydes has been accomplished. The use of iminium catalysis has provided a new strategy for the enantioselective addition of 2-silyloxy furans to unsaturated aldehydes to generate a variety of butenolide systems, an important chiral synthon found among many natural isolates. The (2S,5S)-5-benzyl-2-tert-butyl-imidazolidinone amine catalyst has been found to mediate the conjugate addition of a wide variety of substituted and unsubstituted silyloxy furans to unsaturated aldehydes. A diverse range of aldehyde substrates can be accommodated in this new organocatalytic transformation. Application of this new asymmetric technology to the enantioselective total synthesis of spiculisporic acid and the corresponding 5-epi-spiculisporic acid analogue is also discussed.
349 citations
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347 citations
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TL;DR: The utility of the protocol is shown for the total synthesis of 140-aa-long α-synuclein, a protein that has an important role in the development of Parkinson's disease.
Abstract: This protocol provides a detailed procedure for the chemical synthesis of proteins through native chemical ligation of peptide hydrazides. The two crucial stages of this protocol are (i) the solid-phase synthesis of peptide hydrazides via Fmoc chemistry and (ii) the native chemical ligation of peptide hydrazides through in situ NaNO2 activation and thiolysis. This protocol may be of help in the synthesis of proteins that are not easily produced by recombinant technology and that include acid-sensitive modifications; it also does not involve the use of hazardous HF. The utility of the protocol is shown for the total synthesis of 140-aa-long α-synuclein, a protein that has an important role in the development of Parkinson's disease. The whole synthesis of the target protein α-synuclein in milligram scale takes ~30 working days.
344 citations